3.6. Inhibition of the AMPK Pathway Abolishes the Protective
Effect of CTRP9 on VSMC-Derived Foam Cells
Considering that CTRP9 is an agonist of the AMPK pathway, we aimed to
further explore the role of AMPK in the protective effect of CTRP9. To
this end, the expression of antioxidant enzymes was measured after
incubation with Compound C, a
recognized inhibitor of the AMPK pathway. Pretreatment with Compound C
notably decreased the expression of antioxidant enzymes, indicating that
the AMPK pathway is essential for antioxidative enzyme expression (Fig.
6a and b). Pretreatment with Compound C significantly blocked the
protective effect of CTRP9 against ox-LDL-induced VSMC-derived foam cell
necroptosis, as revealed by the abnormal accumulation of mtROS and
reduction in ΔΨm (Fig. 6c and d). The effects of Compound C on the
necrosomes were examined using western blotting. Inhibition of the AMPK
pathway by Compound C promoted cell necroptosis, as evidenced by the
increased phosphorylation of RIP1 and MLKL as well as the upregulated
expression of RIP3 in VSMC-derived foam cells (Fig. 6e and f).
Collectively, our findings suggest that CTRP9 inhibited ox-LDL-induced
VSMC-derived foam cell necroptosis through the AMPK pathway.